AKT Serine/Threonine Kinases

The AKT serine-threonine kinases are the human homologue to the viral oncogene v-akt. They are also known as protein kinase B (PKB) due to their similarity to protein kinase A (PKA) and protein kinase C (PKC) (Manning BD et al.2007).

Three Akt genes (AKT-1, AKT -2 and AKT -3) have been identified in mammals, and the expression of the different proteins varies in tissues. The serine-threonine kinases Akt-1 and Akt-2 can be detected in almost all tissues. In contrast, the expression of the serine-threonine kinase Akt-3 is limited to some tissue types. In particular, this kinase is highly expressed in the brain, lung, heart and kidney (Koseoglu S et al. 2007).

Akt is an important effector protein in this signaling cascade and is phosphorylated at the cell membrane by phosphoinositide-dependent kinase-1 (PDK1) at the amino acid threonine 308 (Akt-1), 309 (Akt-2), and 305 (Akt-3), respectively, depending on the isoform. For complete activation, phosphorylation at the amino acid serine 473 (Akt-1), 474 (Akt-2) or 472 (Akt-3) is additionally required. This is carried out by phosphoinositide-dependent kinase-2 (PDK2. This is a group of different kinases that can phosphorylate Akt.

They include

• the integrin linked kinase (ILK)
• the Mammalian target-of-rapamycin complex 2(mTORC2)
• the protein kinase Cβ2
• the DNA-dependent protein kinase (DNA-PK)
• and the kinase "Ataxia telangiectasia mutated" (ATM).

AKT is an important effector protein in the PI3K/AKT pathway and is phosphorylated at the cell membrane depending on the isoform by PDK1 at the amino acid threonine 308 (Akt-1), 309 (Akt-2) or 305 (Akt-3). Phosphorylation at the serine position can also occur via autophosphorylation of AKT. Upon activation, AKT kinase regulatesthe activity of various proteins by transferring phosphate groups, which have an effect on cell growth and proliferation, influence cell metabolism, and promote cell survival . More than 100 substrates of Akt have now been identified, characterized by the sequence motif RXRXXS/T-B (R= arginine, X = any amino acid, S= serine, T = threonine and B = amino acid with hydrophobic residues) (Alessi DR et al. 1996). Their functions are only partially known so far. The substrates are phosphorylated at serine or threonine residues and are thereby activated or inhibited (Scheid MPet al. 2001).

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